Prostate-specific antigen peptide-HLA complex (PSA-HLA complex)

The Prostate-specific antigen (PSA) peptide-HLA complex is a molecular target consisting of a processed fragment of the PSA protein (Kallikrein-3) bound to a Major Histocompatibility Complex (MHC) molecule, typically HLA-A*02:01 (UniProt: P07288; PMID: 9191013). PSA is a serine protease primarily expressed by prostatic epithelial cells, and its overexpression is a hallmark of prostate cancer (PMID: 16804171). In the context of immunotherapy, these peptide-MHC complexes are displayed on the surface of tumor cells, where they can be recognized by the T-cell receptor (TCR) of CD8+ cytotoxic T lymphocytes (PMID: 20433375). Therapeutic strategies targeting this complex include cancer vaccines like PROSTVAC (Rilimogene galvacirepvec), which are designed to expand endogenous PSA-specific T cells (PMID: 20433375). Additionally, adoptive cell therapies such as TCR-engineered T cells (TCR-T) are being developed to specifically bind the PSA-HLA complex to induce tumor cell lysis (PMID: 28432105). While PSA is a highly specific biomarker for prostate tissue, the primary therapeutic challenge involves overcoming the immunosuppressive tumor microenvironment and ensuring that the targeted peptides are sufficiently presented on the surface of cancer cells to trigger effective lysis (PMID: 25634619). Monitoring serum PSA levels and HLA-A2 status is critical for patient selection and assessing treatment efficacy (ClinicalTrials.gov: NCT00004604).

Other names

PSA-MHC complexKLK3-HLA complexPSA-derived epitopePSA peptide-MHC complexPSA-pMHC

Activation of CD8+ T-cells to recognize and lyse cells presenting PSA-derived peptides on MHC Class I molecules (PMID: 20433375).